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      Fully automated deep learning-based localization and segmentation of the locus coeruleus in aging and Parkinson’s disease using neuromelanin-sensitive MRI

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          Abstract

          Purpose

          Development and performance measurement of a fully automated pipeline that localizes and segments the locus coeruleus in so-called neuromelanin-sensitive magnetic resonance imaging data for the derivation of quantitative biomarkers of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.

          Methods

          We propose a pipeline composed of several 3D-Unet-based convolutional neural networks for iterative multi-scale localization and multi-rater segmentation and non-deep learning-based components for automated biomarker extraction. We trained on the healthy aging cohort and did not carry out any adaption or fine-tuning prior to the application to Parkinson’s disease subjects.

          Results

          The localization and segmentation pipeline demonstrated sufficient performance as measured by Euclidean distance (on average around 1.3mm on healthy aging subjects and 2.2mm in Parkinson’s disease subjects) and Dice similarity coefficient (overall around \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$71\%$$\end{document} on healthy aging subjects and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$60\%$$\end{document} for subjects with Parkinson’s disease) as well as promising agreement with respect to contrast ratios in terms of intraclass correlation coefficient of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\ge 0.80$$\end{document} for healthy aging subjects compared to a manual segmentation procedure. Lower values ( \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\ge 0.48$$\end{document} ) for Parkinson’s disease subjects indicate the need for further investigation and tests before the application to clinical samples.

          Conclusion

          These promising results suggest the usability of the proposed algorithm for data of healthy aging subjects and pave the way for further investigations using this approach on different clinical datasets to validate its practical usability more conclusively.

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          Most cited references20

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          FreeSurfer.

          FreeSurfer is a suite of tools for the analysis of neuroimaging data that provides an array of algorithms to quantify the functional, connectional and structural properties of the human brain. It has evolved from a package primarily aimed at generating surface representations of the cerebral cortex into one that automatically creates models of most macroscopically visible structures in the human brain given any reasonable T1-weighted input image. It is freely available, runs on a wide variety of hardware and software platforms, and is open source. Copyright © 2012 Elsevier Inc. All rights reserved.
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            Staging of brain pathology related to sporadic Parkinson’s disease

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              Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years.

              Two thousand three hundred and thirty two nonselected brains from 1- to 100-year-old individuals were examined using immunocytochemistry (AT8) and Gallyas silver staining for abnormal tau; immunocytochemistry (4G8) and Campbell-Switzer staining were used for the detection ofβ-amyloid. A total of 342 cases was negative in the Gallyas stain but when restaged for AT8 only 10 were immunonegative. Fifty-eight cases had subcortical tau predominantly in the locus coeruleus, but there was no abnormal cortical tau (subcortical Stages a-c). Cortical involvement (abnormal tau in neurites) was identified first in the transentorhinal region (Stage 1a, 38 cases). Transentorhinal pyramidal cells displayed pretangle material (Stage 1b, 236 cases). Pretangles gradually became argyrophilic neurofibrillary tangles (NFTs) that progressed in parallel with NFT Stages I to VI. Pretangles restricted to subcortical sites were seen chiefly at younger ages. Of the total cases, 1,031 (44.2%) had β-amyloid plaques. The first plaques occurred in the neocortex after the onset of tauopathy in the brainstem. Plaques generally developed in the 40s in 4% of all cases, culminating in their tenth decade (75%). β-amyloid plaques and NFTs were significantly correlated (p < 0.0001). These data suggest that tauopathy associated with sporadic Alzheimer disease may begin earlier than previously thought and possibly in the lower brainstem rather than in the transentorhinal region.
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                Author and article information

                Contributors
                max.duennwald@med.ovgu.de
                Journal
                Int J Comput Assist Radiol Surg
                Int J Comput Assist Radiol Surg
                International Journal of Computer Assisted Radiology and Surgery
                Springer International Publishing (Cham )
                1861-6410
                1861-6429
                19 November 2021
                19 November 2021
                2021
                : 16
                : 12
                : 2129-2135
                Affiliations
                [1 ]GRID grid.5807.a, ISNI 0000 0001 1018 4307, Department of Neurology, Faculty of Medicine, , Otto von Guericke University Magdeburg (OVGU), ; Magdeburg, Germany
                [2 ]GRID grid.5807.a, ISNI 0000 0001 1018 4307, Faculty of Computer Science, OVGU, ; Magdeburg, Germany
                [3 ]GRID grid.424247.3, ISNI 0000 0004 0438 0426, German Center for Neurodegenerative Diseases (DZNE), ; Magdeburg, Germany
                [4 ]GRID grid.5807.a, ISNI 0000 0001 1018 4307, Institute of Cognitive Neurology and Dementia Research (IKND), Faculty of Medicine, , OVGU, ; Magdeburg, Germany
                [5 ]GRID grid.83440.3b, ISNI 0000000121901201, Institute of Cognitive Neuroscience, , University College London, ; London, Great Britain UK
                [6 ]GRID grid.418723.b, ISNI 0000 0001 2109 6265, Center for Behavioral Brain Sciences (CBBS), ; Magdeburg, Germany
                Author information
                http://orcid.org/0000-0003-3838-3345
                Article
                2528
                10.1007/s11548-021-02528-5
                8616874
                34797512
                3ae623f7-df37-41b3-9cc6-5464401761cf
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 16 April 2021
                : 21 October 2021
                Funding
                Funded by: Sachsen-Anhalt
                Award ID: I88
                Funded by: FundRef http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Award ID: 425899996-SFB 1436
                Award ID: 425899996-SFB 1436
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100004895, European Social Fund;
                Award ID: ZS/2016/08/80646
                Award Recipient :
                Categories
                Original Article
                Custom metadata
                © CARS 2021

                localization,segmentation,deep learning,locus coeruleus
                localization, segmentation, deep learning, locus coeruleus

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